PAPER

Donepezil for cognitive impairment in Parkinson's disease: a randomised controlled study

D Aarsland¹, K Laake², J P Larsen³ and C Janvin¹

¹ Section of Geriatric Psychiatry, Psychiatric Hospital of Rogaland, Stavanger, Norway
² Department of Geriatric Medicine, Ullevål Hospital, Oslo, Norway
³ Department of Neurology, Central Hospital of Stavanger, Norway

Correspondence to:
Correspondence to:
Dr D Aarsland, Section of Geriatric Psychiatry, Psychiatric Hospital of Rogaland, Arm. Hansen v 20, 4095 Stavanger, Norway;
aarsland{at}netpower.no

Objective: To study the safety and efficacy of the cholinesterase inhibitor donepezil in patients with Parkinson's disease (PD) and cognitive impairment.

Methods: This was a double blind, randomised and placebo controlled, crossover study in which 14 patients with PD and cognitive impairment received donepezil (5 or 10 mg per day) or matching placebo during two sequential periods lasting 10 weeks each. The primary outcome measures were the mini mental state examination (MMSE) score, the clinician's interview based impression of change plus caregiver input (CIBIC+) score, and the motor subscale of the unified Parkinson's disease rating scale (UPDRS).

Results: Two patients on donepezil (14%) dropped out after one and four weeks of the first treatment period because of peripheral cholinergic side effects, otherwise the adverse effects were few and not severe. Carryover or residual effects were not observed. Parkinsonism did not increase during donepezil treatment. After 10 weeks of treatment, the mean MMSE score was increased by 2.1(SD 2.7) points on donepezil and 0.3 (SD 3.2) points on placebo, and the CIBIC+ score was 3.3 (SD 0.9) on donepezil and 4.1 (SD 0.8) on placebo. Statistical analysis of the repeated measurements and crossover study design showed significant effects of donepezil compared with placebo for MMSE (p=0.013) and CIBIC+ (p=0.034). Five (42%) patients on donepezil and two (17%) on placebo were rated as improved on the basis of the CIBIC+ score.

Conclusions: Donepezil improves cognition, and seems to be well tolerated and not to worsen parkinsonism in patients with cognitive impairment.

Keywords: Parkinson's disease; cognitive impairment; donepezil

Abbreviations: PD, Parkinson's disease; MMSE, mini mental state examination; UPDRS, unified Parkinson's disease rating scale; NPI, neuropsychiatric inventory; DLB, dementia with Lewy bodies

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Grace, J, Amick, M M, Friedman, J H (2009). A double-blind comparison of galantamine hydrobromide ER and placebo in Parkinson disease. J. Neurol. Neurosurg. Psychiatry 80: 18-23 [Abstract] [Full Text]  
• Lee, P. H., Yong, S. W., An, Y.-S. (2008). Changes in Cerebral Glucose Metabolism in Patients with Parkinson Disease with Dementia After Cholinesterase Inhibitor Therapy. JNM 49: 2006-2011 [Abstract] [Full Text]  
• Chen, J. J., Trombetta, D. P., Fernandez, H. H. (2008). Palliative Management of Parkinson Disease: Focus on Nonmotor, Distressing Symptoms. Journal of Pharmacy Practice 21: 262-272 [Abstract]  
• Weintraub, D., Hurtig, H. I. (2007). Presentation and Management of Psychosis in Parkinson's Disease and Dementia With Lewy Bodies. Am. J. Psychiatry 164: 1491-1498 [Full Text]  
• Lippa, C. F., Duda, J. E., Grossman, M., Hurtig, H. I., Aarsland, D., Boeve, B. F., Brooks, D. J., Dickson, D. W., Dubois, B., Emre, M., Fahn, S., Farmer, J. M., Galasko, D., Galvin, J. E., Goetz, C. G., Growdon, J. H., Gwinn-Hardy, K. A., Hardy, J., Heutink, P., Iwatsubo, T., Kosaka, K., Lee, V. M.-Y., Leverenz, J. B., Masliah, E., McKeith, I. G., Nussbaum, R. L., Olanow, C. W., Ravina, B. M., Singleton, A. B., Tanner, C. M., Trojanowski, J. Q., Wszolek, Z. K., for the DLB/PDD Working Group, (2007). DLB and PDD boundary issues: Diagnosis, treatment, molecular pathology, and biomarkers. Neurology 68: 812-819 [Abstract] [Full Text]  
• Ferreri, F., Agbokou, C., Gauthier, S. (2006). Recognition and management of neuropsychiatric complications in Parkinson's disease. CMAJ 175: 1545-1552 [Abstract] [Full Text]  
• Burns, A., O'Brien, J. (2006). Clinical practice with anti-dementia drugs: a consensus statement from British Association for Psychopharmacology. J Psychopharmacol 20: 732-755 [Abstract]  
• Cubo, E., Shannon, K. M., Tracy, D., Jaglin, J. A., Bernard, B. A., Wuu, J., Leurgans, S. E. (2006). Effect of donepezil on motor and cognitive function in Huntington disease.. Neurology 67: 1268-1271 [Abstract] [Full Text]  
• Miyasaki, J. M., Shannon, K., Voon, V., Ravina, B., Kleiner-Fisman, G., Anderson, K., Shulman, L. M., Gronseth, G., Weiner, W. J. (2006). Practice Parameter: evaluation and treatment of depression, psychosis, and dementia in Parkinson disease (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology.. Neurology 66: 996-1002 [Abstract] [Full Text]  
• Samuel, M., Maidment, I., Boustani, M., Fox, C. (2006). Clinical management of Parkinson's disease dementia: pitfalls and progress. Adv. Psychiatr. Treat. 12: 121-129 [Abstract] [Full Text]  
• Cummings, J L (2005). Cholinesterase inhibitors for treatment of dementia associated with Parkinson's disease. J. Neurol. Neurosurg. Psychiatry 76: 903-904 [Full Text]  
• Ravina, B, Putt, M, Siderowf, A, Farrar, J T, Gillespie, M, Crawley, A, Fernandez, H H, Trieschmann, M M, Reichwein, S, Simuni, T (2005). Donepezil for dementia in Parkinson's disease: a randomised, double blind, placebo controlled, crossover study. J. Neurol. Neurosurg. Psychiatry 76: 934-939 [Abstract] [Full Text]  
• Adler, C. H., Thorpy, M. J. (2005). Sleep issues in Parkinson's disease. Neurology 64: S12-S20 [Abstract] [Full Text]  
• Chow, T. (2005). Rivastigmine modestly improves dementia associated with Parkinson's disease, but has important adverse effects. Evid. Based Ment. Health 8: 41-41 [Full Text]  
• Lewis, S J G, Foltynie, T, Blackwell, A D, Robbins, T W, Owen, A M, Barker, R A (2005). Heterogeneity of Parkinson's disease in the early clinical stages using a data driven approach. J. Neurol. Neurosurg. Psychiatry 76: 343-348 [Abstract] [Full Text]  
• Mosimann, U. P., Mather, G., Wesnes, K. A., O'Brien, J. T., Burn, D. J., McKeith, I. G. (2004). Visual perception in Parkinson disease dementia and dementia with Lewy bodies. Neurology 63: 2091-2096 [Abstract] [Full Text]  
• Emre, M., Aarsland, D., Albanese, A., Byrne, E. J., Deuschl, G., De Deyn, P. P., Durif, F., Kulisevsky, J., van Laar, T., Lees, A., Poewe, W., Robillard, A., Rosa, M. M., Wolters, E., Quarg, P., Tekin, S., Lane, R. (2004). Rivastigmine for Dementia Associated with Parkinson's Disease. NEJM 351: 2509-2518 [Abstract] [Full Text]  
• Krupp, L. B., Christodoulou, C., Melville, P., Scherl, W. F., MacAllister, W. S., Elkins, L. E. (2004). Donepezil improved memory in multiple sclerosis in a randomized clinical trial. Neurology 63: 1579-1585 [Abstract] [Full Text]  
• Wint, D. P., Okun, M. S., Fernandez, H. H. (2004). Psychosis in Parkinson's Disease. J Geriatr Psychiatry Neurol 17: 127-136 [Abstract]  
• Aarsland, D., Mosimann, U. P., McKeith, I. G. (2004). Role of Cholinesterase Inhibitors in Parkinson's Disease and dementia with Lewy Bodies. J Geriatr Psychiatry Neurol 17: 164-171 [Abstract]  
• Marsh, L., Williams, J. R., Rocco, M., Grill, S., Munro, C., Dawson, T. M. (2004). Psychiatric comorbidities in patients with Parkinson disease and psychosis. Neurology 63: 293-300 [Abstract] [Full Text]  
• Burton, E. J., McKeith, I. G., Burn, D. J., Williams, E. D., O'Brien, J. T. (2004). Cerebral atrophy in Parkinson's disease with and without dementia: a comparison with Alzheimer's disease, dementia with Lewy bodies and controls. Brain 127: 791-800 [Abstract] [Full Text]  
• Shults, C. W. (2003). Treatments of Parkinson Disease: Circa 2003. Arch Neurol 60: 1680-1684 [Abstract] [Full Text]  
• Miyasaki, J. M., Shannon, K., Voon, V., Ravina, B., Kleiner-Fisman, G., Anderson, K., Shulman, L. M., Gronseth, G., Weiner, W. J. (2006). Practice Parameter: evaluation and treatment of depression, psychosis, and dementia in Parkinson disease (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology.. Neurology 66: 996-1002 [Abstract] [Full Text]